Synthesis, drug release and targeting behaviors of Novel Folated Pluronic F87/poly(lactic acid) block copolymer

摘要

Novel Folated Pluronic F87/poly(lactic acid) block copolymer (FA-F87-PLA) was synthesized by two step reactions. The self-assembling behavior of FA-F87-PLA block copolymer in aqueous solutions was examined by fluorescence measurement, Dynamic Light Scattering (DLS) and Transmission Electron Microscopic (TEM) techniques. The morphology of FA-F87-PLA nanoparticles was found to be spherical micelles. Paclitaxel (PTX) loaded in FA-F87-PLA nanoparticles shows an initial burst release in the first 11 h and followed by a slow release. The in vitro targeting behavior of FA-F87-PLA nanoparticles against OVCAR-3 (folate receptor positive) was investigated by 3-(4,5-Dimethylthiazol-w2-yl)-2,5-diphenyl tetrazolium bromide (MTT) tests. MU results show that the anticancer effect of PTX in FA-F87-PLA nanoparticle over OVCAR-3 cells was stronger than that of PTX in nontargeted PLA-F87-PLA nanoparticle under the specific targeting interaction between folate groups on the surface of FA-F87-PLA nanoparticles and folate receptor on the surface of OVCAR-3 cells. The targeting behaviors of FA-F87-PLA nanoparticles were further confirmed by fluorescence microscopy (FM) technique. The intracellular distribution of FA-F87-PLA nanoparticles was also studied using a triple-labeling method. It was observed that FA-F87-PLA nanoparticles are mainly localized within the cytoplasm of OVCAR-3 cells. (C) 2015 Elsevier Ltd. All rights reserved.